Abstract
BackgroundSince both the antibacterial effects and common adverse effects of colistin are concentration-dependent, determination of the most appropriate dosage regimen and administration method for colistin therapy is essential to ensure its efficacy and safety. We aimed to establish a rapid and simple high-performance liquid chromatography (HPLC)-based system for the clinical determination of colistin serum concentrations.MethodsExtraction using a solid-phase C18 cartridge, derivatisation with 9-fluorenylmethyl chloroformate, and elution with a short reversed-phase Cl8 column effectively separated colistin from an internal standard. The HPLC apparatus and conditions were as follows: analytical column, Hydrosphere C18; sample injection volume, 50 μL; column temperature, 40 °C; detector, Shimadzu RF-5300 fluorescence spectrophotometer (excitation wavelength, 260 nm; emission wavelength, 315 nm); mobile phase, acetonitrile/tetrahydrofuran/distilled water (50,14,20, v/v/v); flow-rate, 1.6 mL/min.ResultsThe calibration curves obtained for colistin were linear in the concentration range of 0.10–8.0 μg/mL. The regression equation was y = 0.6496× − 0.0141 (r2 = 0.9999). The limit of detection was ~ 0.025 μg/mL, and the assay intra- and inter-day precisions were 0.87–3.74% and 1.97–6.17%, respectively. The analytical peaks of colistin A, colistin B, and the internal standard were resolved with adequate peak symmetries, and their retention times were approximately 8.2, 6.8, and 5.4 min, respectively. Furthermore, the assay was successfully applied to quantify the plasma colistin levels of a haemodialysis patient.ConclusionThe assay is a simple, rapid, accurate, selective, clinically applicable HPLC-based method for the quantification of colistin in human plasma.
Highlights
Since both the antibacterial effects and common adverse effects of colistin are concentrationdependent, determination of the most appropriate dosage regimen and administration method for colistin therapy is essential to ensure its efficacy and safety
These infections have become increasingly difficult to treat with standard agents because of the evolution of a wide variety of resistance mechanisms; colistin has re-emerged as a treatment of choice for Gram-negative pathogens, including multidrug-resistant Pseudomonas aeruginosa (MDRP), a virulent hospital-acquired infection [2,3,4,5,6]
We examined the application of this system to measure the colistin concentration in a plasma sample obtained from a haemodialysis patient
Summary
Since both the antibacterial effects and common adverse effects of colistin are concentrationdependent, determination of the most appropriate dosage regimen and administration method for colistin therapy is essential to ensure its efficacy and safety. Colistin exhibits a number of common adverse effects, including nephrotoxicity and neurotoxicity, which are concentration-dependent. This has led to justifiable concerns that the current recommended dosage excessively increases the risk of such adverse effects in patients [10,11,12]. The establishment of a simple and rapid clinically applicable measurement system for assessing colistin concentrations is of particular importance in hospitals. Such a system could be employed to determine the appropriate dosage regimen for colistin therapy to ensure its efficacy and safety
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